HSVTK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK.
Oncol Rep
; 40(2): 682-692, 2018 Aug.
Article
en En
| MEDLINE
| ID: mdl-29845211
ABSTRACT
Retinoblastoma is an severe ophthalmic disease and the most common type intraocular malignant tumor, particularly in infants. Currently, few drugs and therapies are available. Gene therapy has been considered to be a potential treatment to cure cancer effectively and Herpes simplex virus type 1 thymidine kinase/ganciclovir (HSVTK/GCV) is one type of suicide gene therapy that has been extensively studied. Numerous in vitro and in vivo studied have shown that this system can kill tumor cells, including liver and lung cancer cells. GCV is used as an antiviral drug, and the thymidine kinase, HSVTK can phosphorylate GCV to GCVTP, a competitive inhibitor of DNA synthesis, instead of guanine5'triphosphate in the process of DNA synthesis. This process prevents DNA chain elongation causing cell death via apoptosis. However, the toxic effects of HSVTK/GCV on retinoblastoma cells remain unknown, and the molecular mechanisms of its therapeutic effects have not been fully elucidated. Our results suggest that HSVTK/GCV can significantly cause the death of retinoblastoma cell lines, HXORB44 and Y79. Further studies have reported that this cell death is induced by the inhibition of autophagy by activating the MAPK/ERK (mitogenactivated protein kinase/ERK) signaling pathway. The mTOR inhibitor Torin1 can partially block the toxic effects of HSVTK/GCV on HXORB44 cells. The above results demonstrate that the mechanism undertaken by HSVTK/GCV to exhibit therapeutic effects mechanism may inhibit autophagy by activating MAPK/ERK. The findings of the present study may provide novel insight for the exploration of HSVTK/GCV in the treatment of retinoblastoma.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
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Retinoblastoma
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Autofagia
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Timidina Quinasa
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Ganciclovir
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Proteínas Quinasas Activadas por Mitógenos
/
Sistema de Señalización de MAP Quinasas
Límite:
Humans
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2018
Tipo del documento:
Article